Determination of glucose concentration has applications in clinical settings, such as for the day-to-day monitoring of glucose levels in individuals in whom glucose homeostasis is not maintained (e.g., in diabetes or hypoglycemia) and in biomedical research.
Current methods for determining glucose concentrations include various colorimetric reactions, measuring a spectrophotometric change in the property of any number of products in a glycolytic cascade or measuring the oxidation of glucose using a polarographic glucose sensor. For example, U.S. Pat. No. 4,401,122 discloses an in vivo method for measuring glucose, which involves placing an enzyme (e.g., glucose oxidase) either in or under the skin and detecting the enzymatic reaction product (e.g., oxygen) directly through the skin using polarographic or enzyme electrodes. The amount of enzymatic reaction product detected is a measure of the amount of substrate.
Although conventional assays have proven reliable, the reagents on which they rely become exhausted in the presence of glucose. Therefore, these assays require the use of disposable sticks or replaceable cartridges, which can be expensive and inconvenient for the active user.
Meadows and Schultz describe another method by which blood glucose levels can be determined using optical means. They describe a fiber optic glucose sensor based on the competitive binding of glucose and fluorescein-labelled dextran (FITC-dextran) to rhodamine-labelled concanavalin A (Rh-Con A), Meadows, D. and J. S. Schultz, Talanta, 35:145-150 (1988).
The Meadows and Schultz optical sensor is attended by many problems, which means it is of limited use in a clinical setting or in monitoring blood glucose levels in individuals on a day to day basis. First, as mentioned in the article, the sensor can only detect glucose concentrations up to 2.00 mgs/ml. Although the normal physiologic blood glucose concentration in man is approximately 1.00 mg/ml., the concentration of glucose in diabetic blood can often exceed 3.00-4.00 mg/ml., which is well beyond the upper limit of the sensor described.
Second, Meadow's and Schultz's sensor has a short life because, as mentioned in the article, the dextran aggregates and becomes precipitated. Third, only 45% of the fluorescence is quenched using the Meadows and Schultz optical sensor. This effect may not be dramatic enough to be detected.
Finally, the in vivo use of a fiber optic is clinically impractical because in order to work, it must pierce the skin. Therefore, it requires an invasive technique and puts the patient at significant risk for developing serious infection. This is particularly true in diabetic patients who are known to have reduced resistance to infection.
An ideal glucose sensor should be capable of detecting a wide range of glucose concentrations (e.g., concentrations ranging from 0.5 to 5.00 mg/ml.). It should also be reliable, reusable and easy to use. In addition, an in vivo sensor should be non-invasive. Such a sensor would be of great value in markedly improving therapy in diabetic patients. It would also have a number of other research and clinical applications.